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WO1996013193A2 - Dispositif non effractif et procede de determination quantitative d'oxydants et/ou d'antioxydants presents dans la peau - Google Patents

Dispositif non effractif et procede de determination quantitative d'oxydants et/ou d'antioxydants presents dans la peau Download PDF

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Publication number
WO1996013193A2
WO1996013193A2 PCT/US1995/013550 US9513550W WO9613193A2 WO 1996013193 A2 WO1996013193 A2 WO 1996013193A2 US 9513550 W US9513550 W US 9513550W WO 9613193 A2 WO9613193 A2 WO 9613193A2
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WO
WIPO (PCT)
Prior art keywords
skin
test solution
subject
solution
container
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1995/013550
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English (en)
Other versions
WO1996013193A3 (fr
Inventor
Ron Kohen
David Fanberstein
Oren Tirosh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Yissum Research Development Co of Hebrew University of Jerusalem
Original Assignee
Yissum Research Development Co of Hebrew University of Jerusalem
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yissum Research Development Co of Hebrew University of Jerusalem filed Critical Yissum Research Development Co of Hebrew University of Jerusalem
Priority to AU40060/95A priority Critical patent/AU4006095A/en
Priority to US08/817,222 priority patent/US6108570A/en
Publication of WO1996013193A2 publication Critical patent/WO1996013193A2/fr
Publication of WO1996013193A3 publication Critical patent/WO1996013193A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1477—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14542—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring blood gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • A61B5/442—Evaluating skin mechanical properties, e.g. elasticity, hardness, texture, wrinkle assessment

Definitions

  • the invention relates to a non-invasive device and method for the quantitative determination of the level of oxidants and/or antioxidants in the skin.
  • Exposure of humans to free radicals is not limited to the endogenous oxygen free radicals, but also includes exogenous sources.
  • Various chemicals in agricultural use can serve as free radical generation systems, as in the case of the herbicide Paraquat.
  • Other chemicals aloxan, isouramil, cigarette smoke, air pollutants, carcinogenic and mutagenic compounds and many drugs
  • Free radicals have been shown to play an important role in the initiation and patho- genesis of, inter alia, inflammations, autoimmune diseases, brain degenerative diseases (Parkinson, Wilson, epilepsy), and eye diseases (cataract and retinopathy) .
  • These reactive species have also been demonstrated to be involved in ischemic and post-ischemic damage to the heart, brain and gastrointestinal tract.
  • oxygen free radicals take part in cancer, aging and aging- related diseases.
  • an antioxidant includes compounds which can cope with oxidative stress in various mechanisms. These mechanisms include: compounds which donate hydrogen to the damaged target, compounds which can scavenge free radicals, compounds which can bind the oxidants and remove them from the target, compounds which can convert reactive species to nonreactive metabolites, and reducing compounds which can react with oxidants.
  • the various anti ⁇ oxidants may be classified into two main groups: the enzymatic group of antioxidants and the low molecular weight antioxidants (LMWA) .
  • the antioxidant enzymes include the enzymes superoxide dismutase, catalase and peroxidase.
  • the LMWA include compounds which are not synthesized by humans but are present in the diet, such as ascorbic acid (vitamin C), tocopherol (vitamin E) and compounds which can be sy-.tihesized by humans such as glutathione (GSH), carnosine (...i antioxidant present in the brain and muscle), uric acid and others. Most of the compounds in this group are reducing age/its which can react with the oxidants.
  • lipid peroxidation process is of major importance.
  • the occurrence of lipid peroxidation in biological membranes causes impairment of membrane functioning, decreased fluidity, inactivation of membrane-bound receptors and enzymes, and increased non ⁇ specific permeability to ions such as Ca(II).
  • Peroxidation is initiated by the attack of any chemical species that has sufficient reactivity to abstract a hydrogen atom from a methylene carbon in the side chain.
  • the hydrogen atom is a free radical and its removal leaves behind an unpaired electron on the carbon atom to which it was originally a t tached.
  • the resulting carbon centered radical (L * ) can have several fates, but the most likely one in aerobic cells is that it will undergo molecular rearrangement, followed by a reaction with molecular oxygen to yield a peroxy radical (I- 0 ' ) .
  • Peroxy radicals can combine with each other or they can attack membrane proteins, but they are also capable of abstracting hydrogen from adjacent fatty acid side chains in a membrane and in so doing propagate the chain reaction of lipid peroxidation. The result of this hydrogen atom abstraction is the production of lipid hydroperoxide (ROOH).
  • lipid peroxidation status in food products is important for the estimation of shelf life (for food products) and in biological systems for assessing the clinical condition of the organism. It has been shown that an increase in the oxidation of lipids correlates with the aging process and with pathological events in the cell. The measurement of the lipid peroxidation process and products in human materials is probably the evidence most frequently quoted in support of the involv ent of free radicals reac ⁇ tions in tissue damage by disease. Oxidation of lipids can be measured at different stages, including (1) measurement of losses of unsaturated fatty acid; (2) measurement of primary peroxidation products; and (3) measurement of secondary carbonyls and hydrocarbon gases. Search of the scientific literature reveals that there is no method to evaluate lipid peroxidation of animal skin by a non-invasive procedure.
  • One of the major problems in this field of free radicals and antioxidants is the evaluation of the ability of a certain biological tissue or fluid (blood, CSF, saliva, sperm, etc.) to cope with the oxidative stress and to prevent the biolo ⁇ gical damage.
  • the existing methods are based on the measure ⁇ ment and quantification of a specific compound or several compounds in body tissue or the determination of the concentration of a compound or several compounds following exposure of the tissue or the animal to oxidative stress. These methods are insufficient as they give only partial information on the tissue antioxidant status.
  • the epidermis provides the first line of defense against oxidative stress and reactive oxygen species. It has been shown that the surface of the skin is equipped with a defending system which copes with the oxidative stress.
  • the sources of the oxidative stress may be internal (such as infiltration of neutrophils and macrophages into inflamed skin or ischemic process) or external (inonizing radiation; UV light; photochemical reaction products such as superoxide radicals, hydrogen peroxide, hydroxyl radicals; products of the lipid peroxidation process or physical burns).
  • the variety of the antioxidant compounds in intact skin have never been studied in detailed. Non-invasive methods for evaluating the LMWA were not available.
  • the invention relates to a non-invasive device for the quantitative determination of the level of oxidants and/or antioxidants in the skin of a subject comprising a pair of a reference electrode and a working electrode which are connected to electrical voltage measuring means; a test solution container which is open at the bottom side thereof which is placed on the skin of said subject and is releas ⁇ ably but sealingly affixed to the skin by suitable means, filled with a test solution, which solution containing reagent which are capable of being oxidized or reduced by oxidants or antioxidants, respectively, and permitting contact between said test solution and the skin, and is open at the top side thereof through which said electrodes are immersed in said test solution.
  • the invention also relates to a non-invasive method for the quantitative determination of the level of oxidants or anti ⁇ oxidants in the skin of a subject comprising the steps of sealingly affixing to the. skin of the subject a test solution container which is open at the side thereof which is placed on the skin of said subject in a releasable manner by suitable means; filling said container with a suitable test solution, said test solution containing reagents which are capable of being oxidizd or reduced by oxidants or anti ⁇ oxidants present in the skin of said subject, respectively; immersing a pair of a reference electrode and a working electrode, which are connected to electrical voltage measuring means, in said test solution; and measuring the electrical voltage of said test solution at appropriate time points; whereby the concentration of the oxidants or anti ⁇ oxidants in the skin of said subject is determined from the change in the electric potential of said test solution.
  • Figure 1 a schematic illustration of a device according to the invention
  • Figure 2 The changes in potential (E) of a solution of
  • the present invention relates to a non-invasive device for the quantitative determination of the level of oxidants and/or antioxidants in the skin of a subject
  • a non-invasive device for the quantitative determination of the level of oxidants and/or antioxidants in the skin of a subject comprising a pair of a reference electrode and a working electrode which are connected to electrical voltage measuring means; a test solution container which is open at the bottom side thereof which is placed on the skin of said subject and is releas ⁇ ably but sealingly affixed to the skin by suitable means. filled with said test solution and permitting contact between a test solution and the skin, said test solution containing reagent which are capable of being oxidized or reduced by oxidants or antioxidants, respectively, and is open at the top side thereof through which said electrodes are immersed in said test solution.
  • the device according to the invention may further comprising means for accommodating said electrodes and holding the same within said test solution.
  • the reference electrode is preferably a Ag/AgCl electrode or a calomel electrode and said working electrode is preferably a glossy carbon, gold or platinum electrode.
  • the container is preferably an open-sided hollow cylinder and is preferably made from plastics material, such as, e.g.
  • Plexyglass
  • the means for affixing the test solution container to the skin of the subject are any physiologically compatible affixing means, such as e.g., silicone glue.
  • the test solution for the determination of oxidants in the skin is preferably an aqueous iodide or iodide-iodine solution, for example, an aqueous KI or I/I- solution.
  • the test solution for the determination of the level of antioxidants is can be an aqueous iodine solution, an acidic aqueous Fe(III) salt solution, for example an aqueous FeCl- solution, pH ⁇ 2, or an aqueous solution containing chelated Fe(III), for example an aqueous ADP-Fe(III) solution.
  • the device according to the invention is preferably further equipped with means for recording the measured electrical voltage values.
  • the invention also provides a non-invasive method for the quantitative determination of the level of oxidants or antioxidants in the skin of a subject, comprising the steps of: sealingly affixing to the skin of the subject a test solution container which is open at the side thereof which is placed on the skin of said subject in a releasable manner by suitable means; filling said container with a suitable test solution, said test solution containing reagents which are capable of being oxidizd or reduced by oxidants or anti ⁇ oxidants present in the skin of said subject, respectively; immersing a pair of a reference electrode and a working electrode, which are connected to electrical voltage measuring means, in said test solution; and measuring the electrical voltage of said test solution at appropriate time points; whereby the concentration of the oxidants or anti ⁇ oxidants in the skin of said subject is determined from the change in the electric potential of said test solution.
  • the inventors Based on the fact that most of the LMWA are reducing agents (glutathione, ascorbic acid, tocopherols, carnosine, phenols and other small molecules), the inventors have developed a new technique for measuring the total antioxidant capacity of a biological fluid or biological tissue homogenate. This new technique is based on measurements of the redox poten ⁇ tial of redox solutions prior and following exposure to the oxidative stress. It has been previously shown [Kohen, R. , et al., Free Rad. Res. Comms. 17(4) :239-248 (1992); Kohen, R.
  • the present device and method enable, for example, the evaluation of the lipid hydroperoxide (a major primary meta ⁇ bolite in the lipid peroxidation process) in a non-invasive manner. This quantification is based on an in-vitro chemical reaction, a technique used in the food industry for evalua ⁇ ting the peroxide number of unsaturated fatty acid (see below) .
  • Redox potential can be easily measured by the use of volt ⁇ meter.
  • the value obtained is constant and characterized for each electrochemical solution as long as no change occurred in the solution's characteristics (temperature, light, pH, ingredients interactions, concentration, etc). A change in any one of these parameters causes a change in the potential recorded.
  • a solution which contains only the reduced and oxidized forms of the same compounds can be defined as an electro ⁇ chemical cell.
  • Such a cell can be determined by the Nernest equation:
  • T temperature (Kalvin) (room teperature -298 K)
  • n number of electrons participating in the redox reaction
  • a device In the past, in order to evaluate the redox or the oxidation potential of skin, one had to remove the skin, homogenate it and then measure the potential. In the present, non-invasive method, the solution is placed in a well on the surface of the skin. Following a predetermined period or periods of time, the potential of the solution is recorded and by the Nernest equation, knowing the initial concentration of the solution employed, the concentration of the other form pro ⁇ quizd from the interaction of the solution with ingredients present on the surface of the skin can be calculated.
  • One embodiment of a device according to the invention is schema ⁇ tically illustrated in Fig. 1.
  • the bottom open side (3) of a test solution container (1) is releasably but sealingly affixed to the skin of a subject (2) by suitable physiologi ⁇ cally compatible means (not shown).
  • the container then is filled with a suitable test solution (4).
  • a pair of a reference electrode (5) and working electrode (6) are intro ⁇ quizd into the container (1) through the top side (7) there ⁇ of and preferably maintained immersed in the test solution by suitable means (not shown).
  • the electrodes are connected to voltage measuring means (8), which may optionally be equipped with data recording means (9) .
  • the changes in the potential of the solution are recorded at any desired time points.
  • the electrodes are dis ⁇ connected, removed from the test solution container, which, in turn, is released from the skin of the subject.
  • the method of the present invention may be of particular importance for evaluating damage to skin of a subject following exposure to UV or radioactive radiation, burns, inflammation or ischemia by determining decrease of level of antioxidants or increase in level of oxidants in the skin of the subject. This will become apparent from the following examples.
  • Production of iodine is correlated to the ROOH in the tested solution and serves as an indicator for the peroxidation process.
  • a solution of I ⁇ or a solution of KI/Iego of a known concent ⁇ ration is introduced into the well ( Figure 1).
  • the potential of the solution is recorded at 10 min intervals for 60 min. If the surface of the skin (stratum corneum) or the epider ⁇ mis contain a lipid hydroperoxide adduct, iodine is produced. The presence of both species creates an electro ⁇ chemical cell in which the potential can be easily detected.
  • the concentration of iodide is known.
  • the changes in the potential (E) are in correlation with the production of iodine solution (the concentration of the lipid hydroper ⁇ oxide molecules) in the skin (Reaction 2).
  • the concentration of the reduced species correlates to the reducing equivalents in the surface of the area of the skin examined.
  • the reducing equivalents are in correlation with the antioxidant activity on the skin (the reducing equiva ⁇ lents are low molecular weight compounds). Therefore, measurement of the potential (E) of the tested solution can be used as an indication of the antioxidant capacity of the skin.
  • Fe(III) + reducing equivalents in the skin Fe(II) + oxidized equivalents in the skin (antioxidants) Fe(III)/Fe(II) is an electrochemical couple.
  • Oxidative stress such as T-irradiation is known to initiate lipid peroxidation in animal and human tissue as shown in the past. The results obtained by the present non-invasive measurement of the skin support this hypothesis.
  • Lipid peroxidation is often initiated by the use of the peroxy radical initiator AAPH (2-aminopropanedihydroxy- chloride) [Niki, E., et al., Bull. Chem. Soc. Jpn. 59: 497-501 (1986)]. It has been shown in the past that these compounds can produce a flux of peroxy radicals which in turn can initiate lipid peroxidation.
  • AAPH peroxy radical initiator
  • the antioxidant activity of rat skin was determined by the employment of a solution of 0.2M FeCl 3 in a 50 mM KCl buffer pH ⁇ 2.
  • an electrochemical cell is produced (Fe(III)/ Fe(II)).
  • the iron (III) is reduced to iron (II) by reducing equivalents present on surface of the skin and in the epidermis.
  • the reducing equivalents are in correlation with the antioxidant activity as previously shown [Kohen, R., et al., ibid.] and as validated by measuring the antioxidant activity by conventional methods. Fig.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
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  • Molecular Biology (AREA)
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  • Optics & Photonics (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Ce dispositif non effractif de détermination quantitative du taux d'oxydants et/ou d'antioxydants présents dans la peau d'un sujet comprend une électrode de référence ainsi qu'une électrode de travail, lesquelles sont reliées à un dispositif de mesure de la tension électrique. On place sur la peau du sujet, de façon étanche mais amovible, un contenant ouvert sur le côté inférieur, que l'on remplit d'une solution témoin et qui permet à cette solution d'être en contact avec la peau. Ce contenant de solution témoin comprend en outre une ouverture supérieure à travers laquelle on plonge les électrodes dans la solution témoin.
PCT/US1995/013550 1994-10-10 1995-10-10 Dispositif non effractif et procede de determination quantitative d'oxydants et/ou d'antioxydants presents dans la peau Ceased WO1996013193A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU40060/95A AU4006095A (en) 1994-10-10 1995-10-10 Non-invasive device and method for quantitative determination of oxidants and/or antioxidants in the skin
US08/817,222 US6108570A (en) 1995-10-10 1995-10-10 Non-invasive device and method for quantitative determination of oxidants and/or antioxidants in the skin

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL111,228 1994-10-10
IL11122894A IL111228A (en) 1994-10-10 1994-10-10 Non-invasive device and method for quantitative determination of oxidants and/or antioxidants in the skin

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WO1996013193A2 true WO1996013193A2 (fr) 1996-05-09
WO1996013193A3 WO1996013193A3 (fr) 1996-06-27

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2845264A1 (fr) * 2002-10-03 2004-04-09 Fabre Pierre Dermo Cosmetique Dispositif et procede de mesure directe de ph et d'etat d'oxydation
WO2006094529A1 (fr) * 2005-03-11 2006-09-14 Edel Therapeutics S.A. Procede et dispositif pour le pseudotitrage de substances antioxydantes
WO2011162635A1 (fr) * 2010-06-23 2011-12-29 Государственное Образовательное Учреждение Высшего Профессионального Образования "Уpaльcкий Государственный Экономический Университет)) (Ургэу) Procédé pour déterminer de façon non invasive par potentiométrie l'activité oxydante/antioxydante des tissus biologiques et dispositif de sa mise en oeuvre
RU2532406C1 (ru) * 2013-03-22 2014-11-10 Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Уральский федеральный университет имени первого Президента России Б.Н. Ельцина" Способ потенциометрического определения антиоксидантной/оксидантной активности с использованием комплексов металлов

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4821733A (en) * 1987-08-18 1989-04-18 Dermal Systems International Transdermal detection system
US5445147A (en) * 1988-09-08 1995-08-29 Sudor Partners Method and apparatus for determination of chemical species in body fluid

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2845264A1 (fr) * 2002-10-03 2004-04-09 Fabre Pierre Dermo Cosmetique Dispositif et procede de mesure directe de ph et d'etat d'oxydation
WO2004030537A3 (fr) * 2002-10-03 2004-05-13 Fabre Pierre Dermo Cosmetique Dispositif et procede de mesure directe de ph et d'etat d'oxydation
WO2006094529A1 (fr) * 2005-03-11 2006-09-14 Edel Therapeutics S.A. Procede et dispositif pour le pseudotitrage de substances antioxydantes
WO2011162635A1 (fr) * 2010-06-23 2011-12-29 Государственное Образовательное Учреждение Высшего Профессионального Образования "Уpaльcкий Государственный Экономический Университет)) (Ургэу) Procédé pour déterminer de façon non invasive par potentiométrie l'activité oxydante/antioxydante des tissus biologiques et dispositif de sa mise en oeuvre
RU2532406C1 (ru) * 2013-03-22 2014-11-10 Федеральное государственное автономное образовательное учреждение высшего профессионального образования "Уральский федеральный университет имени первого Президента России Б.Н. Ельцина" Способ потенциометрического определения антиоксидантной/оксидантной активности с использованием комплексов металлов

Also Published As

Publication number Publication date
AU4006095A (en) 1996-05-23
IL111228A (en) 1998-10-30
WO1996013193A3 (fr) 1996-06-27
IL111228A0 (en) 1994-12-29

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